APOE_HYSCR
ID APOE_HYSCR Reviewed; 306 AA.
AC P0DUZ2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Hystrix cristata (North African crested porcupine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Hystricidae;
OC Hystrix.
OX NCBI_TaxID=10137;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Johnson J., Muren E., Swofford R., Turner-Maier J., Marinescu V.,
RA Genereux D., Birren B., Karlsson E.K., Lindblad-Toh K.;
RT "The 200 mammals project: sequencing genomes by a novel cost-effective
RT method, yielding a high resolution annotation of the human genome.";
RL Submitted (FEB-2018) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (JUL-2021).
CC -!- FUNCTION: APOE is an apolipoprotein, a protein associating with lipid
CC particles, that mainly functions in lipoprotein-mediated lipid
CC transport between organs via the plasma and interstitial fluids. APOE
CC is a core component of plasma lipoproteins and is involved in their
CC production, conversion and clearance. Apoliproteins are amphipathic
CC molecules that interact both with lipids of the lipoprotein particle
CC core and the aqueous environment of the plasma. As such, APOE
CC associates with chylomicrons, chylomicron remnants, very low density
CC lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but
CC shows a preferential binding to high-density lipoproteins (HDL). It
CC also binds a wide range of cellular receptors including the LDL
CC receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8
CC and the very low-density lipoprotein receptor/VLDLR that mediate the
CC cellular uptake of the APOE-containing lipoprotein particles. Finally,
CC APOE has also a heparin-binding activity and binds heparan-sulfate
CC proteoglycans on the surface of cells, a property that supports the
CC capture and the receptor-mediated uptake of APOE-containing
CC lipoproteins by cells. A main function of APOE is to mediate
CC lipoprotein clearance through the uptake of chylomicrons, VLDLs, and
CC HDLs by hepatocytes. APOE is also involved in the biosynthesis by the
CC liver of VLDLs as well as their uptake by peripheral tissues ensuring
CC the delivery of triglycerides and energy storage in muscle, heart and
CC adipose tissues. By participating in the lipoprotein-mediated
CC distribution of lipids among tissues, APOE plays a critical role in
CC plasma and tissues lipid homeostasis. APOE is also involved in two
CC steps of reverse cholesterol transport, the HDLs-mediated transport of
CC cholesterol from peripheral tissues to the liver, and thereby plays an
CC important role in cholesterol homeostasis. First, it is functionally
CC associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it
CC is enriched in circulating HDLs and mediates their uptake by
CC hepatocytes. APOE also plays an important role in lipid transport in
CC the central nervous system, regulating neuron survival and sprouting.
CC {ECO:0000250|UniProtKB:P02649}.
CC -!- SUBUNIT: Homotetramer. May interact with ABCA1; functionally associated
CC with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-
CC beta peptide; the interaction is extremely stable in vitro but its
CC physiological significance is unclear. May interact with MAPT. May
CC interact with MAP2. In the cerebrospinal fluid, interacts with secreted
CC SORL1. {ECO:0000250|UniProtKB:P02649}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}.
CC Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is associated
CC with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL
CC lipoproteins. Lipid poor oligomeric APOE is associated with the
CC extracellular matrix in a calcium- and heparan-sulfate proteoglycans-
CC dependent manner. Lipidation induces the release from the extracellular
CC matrix. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: APOE exists as multiple glycosylated and sialylated glycoforms
CC within cells and in plasma. The extent of glycosylation and sialylation
CC are tissue and context specific. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: Glycated in plasma VLDL. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P02649}.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC {ECO:0000305}.
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DR EMBL; PVJO010000840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0034364; C:high-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0042157; P:lipoprotein metabolic process; IEA:InterPro.
DR InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 1.
PE 3: Inferred from homology;
KW Chylomicron; Extracellular matrix; Glycoprotein; HDL; Heparin-binding;
KW Lipid transport; Lipid-binding; Oxidation; Phosphoprotein; Repeat;
KW Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..306
FT /note="Apolipoprotein E"
FT /id="PRO_0000454016"
FT REPEAT 81..102
FT /note="1"
FT REPEAT 103..124
FT /note="2"
FT REPEAT 125..146
FT /note="3"
FT REPEAT 147..168
FT /note="4"
FT REPEAT 169..190
FT /note="5"
FT REPEAT 191..212
FT /note="6"
FT REPEAT 213..230
FT /note="7"
FT REPEAT 231..252
FT /note="8"
FT REGION 81..252
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 159..169
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 211..280
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 268..280
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 163..166
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 226..233
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 144
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 306 AA; 34835 MW; E1DEAAA16D5B1377 CRC64;
MKVLWAVLVV TLLAGCQADV EPALEVGEPA PEVREPAMWQ SGQPWELALG RFWDYLRWVQ
TLSDQVQEEL LSSQVTQELT VLMEDTMKEV KAYKSELEQE LGPMAEDTKA RLSKELQAAQ
ARLGADMEEV RNRLTQYRSE VQTMLGQSAE ELRARLASHL RKLRKRLLRD AEDLQKRLAV
YKAGAQEGAE RGVSAIRERL GSLVEQGRLR AAQTSQPLRE RAQAWGERLR GRLEEVGGQA
RDRLDVVREQ MEEVRAKVEE QAEAFQARLK GWFEPVVEDM RRQWAELIEK VQVAVGASTP
APSEKH
